| Eligibility |
Inclusion Criteria:
1. Patients voluntarily participate in this study and sign informed consent;
2. Age 18-75 years, including 18 and 75 years old, male or female;
3. Patients with histologically confirmed locally advanced esophageal squamous cell
carcinoma with a clinical stage of stage II-IVa that is inoperably resectable
(including unresectable, or has contraindications to surgery or refuses surgery)
(according to the 8th edition AJCC stage, the pre-treatment clinical stage is:
cT1N2-3M0, cT2-4bN0-3M0);
4. the presence of measurable and/or non-measurable lesions that meet the definition of
the Efficacy Evaluation Criteria for Solid Tumors (RECIST1.1);
5. Have not received systemic antineoplastic therapy (including but not limited to
systemic chemotherapy, molecularly targeted therapy, immunotherapy, biological
therapy, topical therapy, and other investigational therapies)
6. ECOG: 0~1 point
7. Fresh or archived tumor tissue samples within 6 months (fresh samples preferred) must
be provided for biomarker (such as PD-L1) analysis, the sample type is FFPE tumor
tissue block or at least 5 unstained, 3-5 µm thick FFPE tumor tissue section, for
subjects who cannot provide tissue samples that meet the above requirements, they can
discuss with the sponsor to determine whether to enroll;
8. Expected survival= 3 months;
9. The function of vital organs meets the following requirements (no blood components and
cell growth factors are allowed 2 weeks before starting screening tests):
1. Absolute neutrophil count (ANC) =1.5×109/L;
2. platelets= 100×109/L;
3. hemoglobin= 9g/dL;
4. serum albumin= 2.8 g/dL;
5. Total bilirubin = 1.5 × ULN, ALT, AST and/or AKP=2.5 × ULN;
6. Serum creatinine =1.5 × ULN or creatinine clearance = 60 mL/min (calculated
according to the Cockcroft-Gault formula, see Annex II);
7. International normalized ratio (INR) and activated partial thromboplastin time
(APTT) =1.5× ULN (can be screened for anticoagulation at a stable dose such as
low molecular weight heparin or warfarin and INR within the expected therapeutic
range of anticoagulants);
10. Female subjects of childbearing potential should have a urine or serum pregnancy test
within 72 hours prior to receiving the first study drug administration and demonstrate
a negative testament,and be willing to use an effective method of contraception during
the trial period to 3 months after the last dose. For male participants whose partner
is a woman of childbearing age, effective methods of contraception should be used
during the trial and up to three months after the last dose
Exclusion Criteria:
1. history of surgery for esophageal cancer;
2. history of previous fistula due to primary tumor invasion;
3. a higher risk of gastrointestinal bleeding, esophageal fistula, or esophageal
perforation;
4. participants with poor nutritional status with a BMI of less than 18.5 kg/m2 or a
PG-SGA score of =9;
5. have undergone major surgery or severe trauma within 4 weeks prior to the first use of
the study drug;
6. presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring
repeated drainage;
7. Have received or are currently receiving any of the following treatments:
1. Anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted
therapy;
2. Have received any investigational drug within 4 weeks prior to the first use of
the investigational drug;
3. Participants who require systemic therapy with corticosteroids (> 10 mg
prednisone equivalent per day) or other immunosuppressants within 2 weeks prior
to the first study drug, except for local inflammation of the esophagus and for
the prevention of allergies and nausea and vomiting. In other special
circumstances, it is necessary to communicate with the sponsor. In the absence of
active autoimmune disease, inhaled or topical steroid replacement and
adrenocorticosteroid replacement at a dose > a potent dose of 10 mg/day
prednisone is allowed;
4. Those who have received an antitumor vaccine or have received a live vaccine
within 4 weeks prior to the first dose of the study drug
8. have any active autoimmune disease or history of autoimmune disease (eg, interstitial
pneumonia, uveitis, enteritis, hepatitis, pituitary physitis, vasculitis, myocarditis,
nephritis, hyperthyroidism, hypothyroidism); Except vitiligo or patients with
asthma/allergies of the same age who have recovered and do not require any
intervention in adulthood; Patients with autoimmune-mediated hypothyroidism treated
with stable doses of thyroid replacement hormone and type I diabetes mellitus treated
with stable doses of insulin may be included;
9. a history of immunodeficiency, including a positive HIV test, or other acquired or
congenital immunodeficiency disorders, or a history of organ transplantation and
allogeneic bone marrow transplantation;
10. Subjects with uncontrolled cardiac clinical symptoms or diseases, such as (1) heart
failure with NYHA II and above, (2) unstable angina, (3) myocardial infarction within
1 year, (4) clinically significant supraventricular or ventricular arrhythmias
requiring clinical intervention;
11. Severe infection (CTC AE> grade 2) within 4 weeks prior to the first use of the study
drug, such as severe pneumonia, bacteremia, infection comorbidities, etc. requiring
hospitalization; Baseline chest imaging suggests active lung inflammation, signs and
symptoms of infection present in the 2 weeks prior to first study drug use requiring
oral or intravenous antibiotic therapy, except for prophylactic antibiotics;
12. history of interstitial lung disease, noninfectious pneumonia, pulmonary fibrosis, or
other uncontrolled acute lung disease;
13. Patients with active tuberculosis infection detected by history or CT examination, or
patients with a history of active tuberculosis infection within 1 year prior to
enrollment, or patients with a history of active tuberculosis infection more than 1
year before that have not been formally treated;
14. Participants had active hepatitis B (HBV DNA = 2000 IU/mL or 104 copies/mL), hepatitis
C (positive for hepatitis C antibodies and HCV-RNA above the lower limit of the
assay);
15. Laboratory values of sodium, potassium, and calcium greater than grade 1 were abnormal
in the first 2 weeks of randomization and could not be improved after treatment;
16. known allergy to macromolecular protein preparations, or to any carrelizul component,
or allergy, hypersensitivity or contraindication to paclitaxel or cisplatin or any of
the ingredients used in their preparations;
17. Any other malignancy diagnosed prior to the first use of the study drug, except for
malignancies with a low risk of metastasis and death (5-year survival >90%), such as
adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in
situ;
18. pregnant or lactating women; participants of childbearing potential who are unwilling
or unable to use effective contraception;
19. According to the investigator's judgment, the subject has other factors that may cause
him to be forced to terminate the study halfway, such as other serious diseases
(including psychiatric diseases) that require combined treatment, recent combination
with other serious diseases (such as myocardial infarction, cerebrovascular accident)
considering a high risk of recurrence, serious abnormal laboratory test values, family
or social factors, which may affect the safety of subjects or the collection of trial
data
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